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2-mercaptopropionylglycine

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RADIOBIOLOGICAL ASPECTS

Dose Modification Factor[DMF]: DMF based on LD50/30 :- 1.4 (data from mice study)[1], [2].
1.40-1.65(animal data for Thiola). When combined with aminothiols (AET, MEA, cysteine), DRF of 1.72 could be achieved[3].
Studies related to DMF : MPG at concentration around 0.02mM and 15mM found to have slight radioprotective action. Protection was not found to increase with the increase in concentration of MPG - A study on in vitro mouse L cells[4].
After high doses of radiation, drug became less effective in protecting the tissue[5],[6].
In mouse erythrocytes, MPG did not have any effect on the initial cell depression, but it afforded significant protection at later intervals with sublethal gamma doses (250 R and 500 R); however, after lethal exposure (1000 R) the drug did not show any protective effect [7].
MPG offered protection to mouse liver after whole-body irradiation with 1000 R gamma rays[8] and with 500 R gamma rays to mouse testes both at initial stage of cell damage as well as at the later stage of recovery[9].
At high concentrations of MPG, enhancement of lipid peroxidation was observed instead of reduction following gamma-irradiation at 266.4Gy [10]. A study with MPG has also revealed its radiosensitizing ability under particular circumstances[11]. Decrease in effectiveness of radioprotection by MPG may be contributed to the availability of quantity other than optimum for radioprotection in particular tissue, also to metabolism of MPG to its oxide, disulfide and other derivatives after its administrations [12]. Dose dependent protective effect of 2-MPG on radiation induced mitotic delay in cultures mammalian cell (L-5) is observed [13].
It has been established that this drug, as the Sodium salt, is able to prevent all radiation damage in animals irradiated with lethal or supra lethal doses of various radiation qualities, if applied not only before but within 3-5 h after irradiation[14]
The protection by MPG in mice against lethal IR doses could last at least for more than 3 hours after a intraperitoneal injection[1],[2]
MPG, when given 30 minutes after exposure, was not found to be so effective in radioprotection[15]
Protection offered by MPG at different parameters
60Co-irradiation
Dose of radiation Drug Dose Time of administration of drug DMF Reference
1.5 Gy, 3 Gy, 6 Gy, 9 Gy before irradiation [6]
1000R in 42 minutes 20 mg/kg, IP 15-30 mins before irradiation [8]
1000R in 42 minutes 20 mg/kg, IP 30 mins before irradiation [16]
1000R(25 R/min) 15-30 mins before irradiation [17]
36 R/min 0.5 mg, 1mg 15 mins before irradiation 1.4 [1]
1000 R 0.01mg to 1mg 30 mins before irradiation max protection at 0.5 mg [1]
0.6, 1.2, 2.4 Gy before irradiation [18],[19]
250 R before irradiation [20]
2.2 Gy(sublethal) 20 mg/kg, IP before irradiation [21]
0.6, 1.2 Gy before irradiation [22]
150 R before irradiation [23],[24]
50R, 150R, 250R before irradiation [25]
1500R before irradiation [26]
250R, 500R before irradiation [7]
250R, 500R, 1000R (50 R/min) 20 mg/kg, IP 15-30 mins before irradiation [27]
1.5 Gy before irradiation [28]
2.5Gy, 5Gy, 10 Gy before irradition [29]
1Gy, 2Gy, 4Gy, 6Gy, 8Gy (23.65 Gy/min) 0.408mg eqv. of MPG as 1m LEM(liposomal encapsulated MPG) 30 mins before irradiation [12]
500 R (25 R/min) 20 mg/kg, IP 15-30 mins before irradiation [9]
500R in 19 mins 20mg/kg, IP 30 mins before irradiation [15]
500R in 19 mins 20 mg/kg, IP 15-30 mins after irradiation Not effective [15]
1200R in 40 mins 20 mg/kg,IP 30 mins before irradiation [30]
200R 20-100 mM after irradiation [13]
0.5 Gy, 1.5 Gy, 2.5 Gy before irradiation [31]
0.5Gy, 1.5Gy, 3Gy 4.5Gy, 6Gy (0.72 Gy/min) 15-25 mins before irradiation [5]
500R, 1000R, 1500R before irradiation [32]
500R, 1000R, 1500R (24 R/min) 15-30 mins before irradiation [33]
80-160Gy (40.22 Gy/min) 0.2 mg/ml, 0.5 mg/ml before irradiation [34]
2.5Gy, 5Gy, 10Gy (0.5 Gy/min) 20 mg/kg, IP 15-30 mins before irradiation [35]
0.5Gy, 1Gy, 2Gy (0.5 Gy/min) 20 mg/kg 15-20 mins before irradiation [36]
1000R 10, 20 and 200 mg/kg 15 mins before irradiation [2]
0.5Gy, 1.5Gy, 3Gy, 4.5Gy, 6 Gy (0.72 Gy/min) 20 mg/kg, IP 15-20 mins before irradiation protection at low doses(0.5 Gy, 1.5 Gy) [5]
39 Gy 10 mM 10 mins before irradiation (in oxygen) 1.30 [37]
39 Gy 10 mM 25 mins before irradiation (in oxygen) 1.16 [37]
39 Gy 10 mM 10 mins before irradiation (in anorexia) 1.21 [37]
39 Gy 10 mM 25 mins before irradiation (in anorexia) 0.89 [37]
39 Gy 20 mM 10 mins before irradiation (in oxygen) 1.27 [37]
39 Gy 20 mM 25 mins before irradiation (in oxygen) 1.10 [37]
39 Gy 20 mM 10 mins before irradiation (in anorexia) 1.57 [37]
39 Gy 20 mM 25 mins before irradiation (in anorexia) 0.97 [37]
900 rads 4 hrs before irradiation or 24 hrs after irradiation moderate radioprotection [38]
X-irradiation
Dose of radiation Drug Dose Time of administration of drug DMF Reference
500R (75 R/min) 0.02 mM and 15 mM 15 mins before irradiation [4]
10 Gy 20 mg/kg, IP 1 day after irradiation [39]
3Gy, 19Gy before irradiation [40]
7.60 Gy (LD50/30) 20 mg/kg before irradiation 1.1 [41]
500R 0.01-0.1 mM and 5-60 mM before irradiation [2]
Beta-irradiation from Tritiated water(HTO)
Dose of radiation Drug Dose Time of administration of drug DMF Reference
IP injection of 5microCi/g of HTO 20 mg/kg 15-30 mins before injection of HTO [42]
Fractionation study: Cervical cancer patients receiving conventional fractionation radiotherapy (whole pelvis irradiation; a daily dose of 150 rad, 5 times per week, the total tumor dose being about 6000 rad in the case of radiotherapy alone, or 4050 rad in postoperative cases) as well as MPG 250 mg intravenously 15-30 min before every irradiation, showed statistically significant increase in the leukocyte counts and decrease in chromosome and aberration yields than control group [2].
Radiation source: 60Co- gamma rays [5], [22], [43].
Many animal Studies are reported against sublethal, lethal and supralethal doses of x-ray, gamma and mixed neutron-gamma radiation from an atomic reactor[3].
Beta radiation from tritiated water[42].
UV-radiation[44].
REFERENCES
1. Nagata H, Sugahara T, Tanaka T, Radiation protection by 2-mercaptopropionylglycine in mice, J Radiat. Res, 1972;13,163-166.
http://dx.doi.org/10.1269/jrr.13.163
2. Sugahara T, Horikawa M, Hikita M, Nagata H, Studies on a sulfhydryl radioprotector of low toxicity, Experientia Suppl. 1977;27:53-61.
http://dx.doi.org/10.1007/978-3-0348-5582-2_5
3. Sántha A., Mándi E., Benkó G. and Bodó S. Z. Proceedings: The radioprotective effect of alpha-mercaptopropionylglycine and its combinations on animals, Br J Cancer. 1975 December; 32(6): 768.
http://dx.doi.org/10.1038/bjc.1975.347
4. Hikita M, Horikawa M, Mori T, Analyses of radioprotective action and cytotoxicity of various sulfhydryl compounds in cultured mouse L cells, J Radiat Res. 1975, 16(3):162-72.
http://dx.doi.org/10.1269/jrr.16.162
5. Gupta R. and Devi UP, Protection against radiation induced chromosome injury by sulfhydryl compounds, Acta Radiol Oncol., 1985; 24(5):419-25.
http://informahealthcare.com/doi/pdf/10.3109/02841868509134412
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7. Devi PU, Kumar S, Radioresponse of peripheal blood and its modification by MPG (2-mercaptopropionylglycine) in mice. I. Erythrocytes, Strahlentherapie. 1981; 157(1):63-5.
http://www.ncbi.nlm.nih.gov/pubmed/7210050
8. Saini MR, Saharan BR, Bhartiya HC, Devi PU, Radiation protection of mouse liver by 2-mercaptopropionylglycine, J Radiat Res. 1977;18(3):206-10.
http://dx.doi.org/10.1269/jrr.18.206
9. Saharan BR, Devi PU., Radiation protection of mouse testes with 2-mercaptopropionylglycine, J Radiat Res. 1977; 18(4):308-16.
http://dx.doi.org/10.1269/jrr.18.308
10. Ayene SI, Srivastava PN., Radioprotective effect of 2-mercaptopropionylglycine on radiation induced microsomal lipid peroxidation, Int J Radiat Biol Relat Stud Phys Chem Med. 1985; 48(2):197-205.
http://dx.doi.org/10.1080/09553008514551191
11. Wary KK and Sharan RN, Effect of the radioprotector 2-mercaptopropionyl glycine (MPG) on the radiation inactivation of catalase in vitro, J. Radiat. Res. 1988, 29, 104-109.
http://dx.doi.org/10.1269/jrr.29.104
12. Sharan RN, Alam A, Chakraborty S, Saikia JR, Srivastava PN, 2-Mercaptopropionylglycine affords enhanced radioprotection after a liposome encapsulation, J Radiat Res. 1995;36(1):31-7.
http://dx.doi.org/10.1269/jrr.36.31
13. Kawasaki, Susumu two, Effect of 2-Mercaptopropionyl Glycine (MPG) on Radiation-Induced Mitotic Delay in Cultured Mammalian Cell (L-5), Yamaguchi medicine 1978; 27(1):65-68.
http://petit.lib.yamaguchi-u.ac.jp/G0000006y2j2/metadata/B030027000106
14. Sántha A, Cságoly E, Horváth M., Proceedings of the European Society for Radiation Biology: Radioprotective effectivity of alphamercaptopropionylglycine (Thiola, Meprin) and study of its SH activity, Br J Cancer. 1975; 32(6):767. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025028/pdf/brjcancer00321-0131a.pdf
15. Devi PU and Saini MR, Protection of Mouse Thymus against Cobalt-60 Radiation by 2-Mercaptopropionylglycine (MPG), J. Radiat. Res. 1977, 18, 211-224. http://dx.doi.org/10.1269/jrr.18.211
16. Devi PU, Saini MR, Saharan BR and Bhartiya HC, Radioprotective Effect of 2-Mercaptopropionyl glycine on the Intestinal Crypt of Swiss Albino Mice after Cobalt-60 irradiation, Radiation Research 1979,80, 214-220.
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18. Mathur S, Nandchahal K, Bhartiya HC., Radioprotection by MPG of mice ovaries exposed to sublethal gamma radiation doses at different postnatal ages, Acta Oncol. 1991; 30(8):981-3.
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19. Mathur S, Bhartiya HC, Routh J, Nandchahal, Depletion of ovarian oocytes in sublethally exposed mice to gamma radiation and its modification by 2-mercaptopropionylglycine (MPG), Indian J Exp Biol. 1991;29(1):83-5.
http://www.ncbi.nlm.nih.gov/pubmed/1864626
20. Dev PK, Gupta SM, Goyal PK, Mehta G, Pareek BP., Radioprotective effect of MPG (2-mercaptopropionylglycine) on the postnatal growth of mice irradiated in utero, Strahlentherapie. 1981; 157(8):553-5.
http://www.ncbi.nlm.nih.gov/pubmed/7268824
21. Nandchahal KK, Routh J, Mathur S, Bhartiya HC, Radiation response of plasma protein and albumin of peripheral blood and its modification by MPG (2-Mercaptopropionylglycine) in mice, Strahlenther Onkol. 1990 Apr; 166(4):306-9.
http://www.ncbi.nlm.nih.gov/pubmed/2330547
22. Routh J, Bhartiya HC, Nandchahal KK, Mathur S, Efficacy of 2-mercaptopropionylglycine (MPG): a radioprotector in modifying the gonadal response of whole body irradiated male Swiss albino mice, Radiobiol Radiother (Berl). 1990; 31(3):279-83.
http://www.ncbi.nlm.nih.gov/pubmed/2201057
23. Dev PK, Pareek BP, Gupta SM, Goyal PK, Mehta G, 2-Mercaptopropionylglycine protection against growth-inhibiting effects in utero irradiated mice, Acta Anat (Basel). 1982; 112(3):249-53.
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24. Goyal PK, Kumar S, Dev PK., Radioresponse of postnatal erythrocytes and its modification by MPG (2mercaptopropionylglycine) in mice exposed to gamma radiation in utero, Strahlentherapie, 1982; 158(12):731-3.
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25. Dev PK, Pareek BP, Goyal PK, Mehta G, Gupta SM., Effects of prenatal gamma-radiation on the development of mice and its modification by 2-mercaptopropionylglycine, Acta Anat (Basel). 1983; 116(4):339-45.
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26. Saharan BR, Saini MR, Uma Devi P, MPG protection against radiation sickness and weight loss and its correlation with mortality of mice after whole-body gamma-irradiation, Strahlentherapie. 1981; 157(2):138-40.
http://www.ncbi.nlm.nih.gov/pubmed/7222134
27. Mathur VB, Radioprotective effect of 2-mercaptopropionylglycine on the protein contents of mouse ileum, Current Science 1985; 54(18):929-930.
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28. Pareek BP, Mehta G, Bhartiya HC, Dev PK, Response of developing mouse liver irradiated in utero and its modification by 2-mercaptopropionylglycine, Acta Radiol Oncol. 1983; 22(1):55-60.
http://www.ncbi.nlm.nih.gov/pubmed/6305134
29. Kumar S, Uma Devi P., Radioresponse of peripheral blood and its modification by MPG (2mercaptopropionylglycine) in mice IV total plasma protein, Strahlentherapie. 1983; 159(8):502-4.
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30. Devi PU, Protection of Mouse Intestine against Gamma Irradiation by 2-Mercaptopropionylglycine (MPG), J. Radiat. Res. 1977, 18, 160-163.
http://dx.doi.org/10.1269/jrr.18.160
31. Goyal PK, Dev PK., Radioresponse of fetal testes of mice and its modification by MPG (2mercaptopropionylglycine), Strahlentherapie. 1983; 159(4):239-41.
http://www.ncbi.nlm.nih.gov/pubmed/6857738
32. Devi PU, Saharan BR, Chemical protection of mouse spermatocytes against gamma-rays with 2-mercaptopropionylglycine, Experientia. 1978; 34(1):91-2.
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33. Saini MR, Devi PU, Yadav SS, Radiation protection of bone marrow lymphocytes by 2-mercaptopropionylglycine (MPG), Experientia. 1978 Dec 15; 34(12):1627-8.
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34. Ayene SI, Kale RK, Srivastava PN, Radioprotective effect of 2 mercaptopropionyl glycine on radiation induced lipid peroxidation and enzyme release in erythrocytes, Int. J. Radiat. Biol. 1988; 53(4): 629-639.
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35. Kumar A, Devi PU, Chemoprotection of ovarian follicles of mice against gamma irradiation by MPG (2-mercaptopropionylglycine), J Radiat Res. 1982; 23(3):306-12.
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36. Sharma P. and Saini MR, Modification of Radiation Induced Prenatal Mortality by Cysteamine, MPG and their Combination in Swiss Albino Mice, Ind. J. Nuc. Med. 2003;18(1 & 2): 12-18.
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37. Kobayashi S, Kasuya M, Ishii Y, Takehana M, Sakai K, Suzuki N, Itoi M, Effects of 2-mercaptopropionylglycine on the development of X-ray induced cataract in rats, Curr Eye Res. 1992;11(11):1099-103.
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38. Geist JR, Kafrawy AH, Shupe RE., The effect of MPG on radiation-induced odontogenic tissue metaplasia, Oral Surg Oral Med Oral Pathol., 1988; 65(1):109-13.
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39. Maisin JR, Albert C, Henry A, Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors, Radiation Research. 1993; 135: 332-337.
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40. Gupta ML, Singh RP, Uma Devi P, Protection of mouse liver by 2-mercaptopropionylglycine against beta radiations from injected tritiated water, J Radiat Res. 1979 Dec;20(4):329-37.
41. Giamberrasi l, Jacobs A, Radioprotectants ; In Military Radiobiology edited by James Conklin and Richard Walker, 1987, Academic Press, Florida, Page 292.
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42. Sántha A, Cságoly E, Horváth M., Proceedings of the European Society for Radiation Biology: Radioprotective effectivity of alphamercaptopropionylglycine (Thiola, Meprin) and study of its SH activity, Br J Cancer. 1975; 32(6):767.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025028/pdf/brjcancer00321-0131a.pdf
43. Xia Wei,Sun Wen-xin,Zhang Chang-zheng et al., Preventive and Therapeutic Effect of Tiopronin on Leukopenia Induced by Radiotherapy in Mice, Henan Journal Of Oncology, 2000-04.
http://en.cnki.com.cn/Article_en/CJFDTOTAL-HLZL200004002.htm
44. van den Broeke LT, Beyersbergen van Henegouwen GM, UV-radiation protecting efficacy of thiols, studied with UVA-induced binding of 8-MOP and CPZ to rat epidermal biomacromolecules in vivo, Int J Radiat Biol. 1993;63(4):493-500.
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